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To estimate whether there has been an increase in resident graduates pursuing fellowship training in the currently accredited subspecialties and to compare whether any trend toward subspecialization is similar to those seen in other specialties.This descriptive study examined data from the National Residency Match Program for academic years 2000-2012. Annual comparisons were made between the numbers of residents who either pursued careers in their specialty or were accepted into fellowship training in an accredited subspecialty. We compared the numbers in each group who took the American Board of Obstetrics and Gynecology (ABOG) written board examination and who became board-certified.Although the annual number of residency graduates in obstetrics and gynecology remained essentially the same (1,185 ± 56), the proportion of graduates accepted into fellowships increased steadily in all subspecialties (from 7.0% in 2000 to 19.5% in 2012). All other core specialties saw higher proportions of their graduates pursuing subspecialties except for family medicine. Coincident with rises in fellowship programs and positions was eventual increase in trainees who took the ABOG written examination for the first time in the three established subspecialties (maternal-fetal medicine, gynecologic oncology, reproductive endocrinology and infertility) and who became board-certified.Like with residents in other specialties, more graduates in obstetrics and gynecology are pursuing accredited subspecialty fellowship training, adding to the complexities of workforce planning. The percent of obstetrics and gynecology residents who pursued accredited subspecialty fellowship training was lower than all but one other specialty.

Objective : Our purpose was to study the efficacy of ephedrine versus angiotensin II prophylactic infusions to counter maternal hypotension that occurs during spinal anesthesia at cesarean delivery. Study Design : Healthy pregnant women undergoing elective repeat cesarean delivery at term with spinal anesthesia were randomized either to a control group ( n = 10) or to one of two prophylactic infusion groups: angiotensin II ( n = 10) or ephedrine ( n = 10). Prophylactic infusions were titrated to a maternal diastolic blood pressure 0 to 10 mm Hg above baseline. Maternal and fetal blood samples for angiotensin II levels and acid-base status were obtained. Student's t test, χ 2 , and analysis of variance were used. Results : Mean arterial pressures were maintained after spinal anesthesia in the ephedrine and angiotensin II groups but decreased ( p ≤ 0.05) in the control group. Maternal angiotensin II levels rose with angiotensin II infusions but were unaltered in the other groups. Umbilical artery and vein angiotensin II levels were unaltered by angiotensin II infusions. Mean umbilical artery blood pH was lower ( p ≤ 0.05) in the ephedrine group than in the angiotensin II and control groups. Conclusions : In the healthy term fetus there is an advantage in using angiotensin II to maintain maternal blood pressure during regional anesthesia.

Objective: The mechanism(s) by which magnesium sulfate (MgSO4) functions clinically to prevent eclamptic seizures in severe pregnancy-induced hypertension (PIH) is unknown; however, it has been reported to both enhance and inhibit prostacyclin (PGI2) production by umbilical vein endothelial cells. Because PGI2 is decreased in patients with PIH, we tested the hypothesis that MgSO4 increases vasodilatory prostaglandins [PGI2 and prostaglandin (PG)E2] relative to vasoconstrictor eicosanoids [thromboxane (Tx)A2 and PGF2aL] in patients with PIH.Methods: In 11 women with PIH (28-40 weeks' gestation), MgSO4 was administered i.v. as a 4-g loading dose, followed by 2 g/h continuous infusion. Plasma samples were obtained before and at 2 and 4 h of MgSO4 treatment.Main Outcome Measures: We measured the effects of i.v. MgSO4 on plasma 6-keto-PGF1aL, TxB2 (metabolites of PGI2 and TxA2, respectively), PGE2, and PGF2aL.Results: The control plasma 6-keto-PGF1aL levels and 6-keto-PGF1aL/TxB2 ratios averaged 22038 pg/mL an...

Objective: Normal pregnant women are characterized by decreases in blood pressure and dramatic falls in systemic vascular resistance. This vasodilation is lost in pregnancies complicated by proteinuric hypertension (preeclampsia). Because gamma-amino butyric acid (GABA) is considered to be both an inhibitory neurotransmitter and an antihypertensive amino acid, we hypothesized that GABA levels might increase throughout gestation and might play a role in the vasodilatory alterations observed in normal pregnancy.Methods: Blood samples for measurement of plasma GABA by high-pressure liquid chromatography (HPLC) were obtained from 4 normal nonpregnant women, from 39 pregnant women at various times throughout gestation, and from 5 women with preeclampsia (37-40 weeks).Results: Normal pregnancy was associated with progressive increases (p < 0.01) in plasma GABA levels after the first trimester, reaching maximum values by 27-33 weeks of gestation. In term hypertensive pregnant women, GABA levels were 13 ± 3% lowe...

OBJECTIVES: The null hypothesis of this retrospective literature analysis was that the superiority of laparoscopy over laparotomy to correct infertility resulting from tubal injury has not been proved because of the lack of well-designed comparative studies. The same was true for the correction of infertility caused by minimal and mild endometriosis. STUDY DESIGN: A retrospective review of the English-language literature since 1975 was made to ascertain whether laparoscopic surgical correction of infertility caused by tubal injury and endometriosis resulted in an increased pregnancy rate compared with laparotomy techniques. Complication rates associated with laparoscopy versus laparotomy were also compared. RESULTS: There were almost no adequate studies designed and executed to answer these questions based on criteria established by the United States Preventive Services Task Force. Furthermore, there was no evidence in the reported series that laparoscopic surgical procedures were superior to laparotomy in correcting infertility. The complication rates were similar. There was suggestive, but not yet proven, evidence that laparoscopic surgery with laser techniques may be superior to laparotomy in the management of infertility resulting from moderate and severe endometriosis. CONCLUSION: Although results and complications were similar, the cost in savings with respect to decreased hospital expenses and loss of work time favor the use of laparoscopy over laparotomy when results are similar and not associated with increased risk. What has not been established are costs and work-time losses for minilaparotomy compared with laparoscopy.

Objective: To project the future supply of practicing subspecialists in obstetrics and gynecology based on the most recent numbers of physicians entering fellowships. Methods: A discrete actuarial model was developed, and supply projections were examined using 1999 subspecialty fellowship numbers from the American Board of Obstetrics and Gynecology. Results: The numbers of obstetrician-gynecologists entering subspecialty fellowships in maternal-fetal medicine (MFM) and reproductive endocrinology–infertility (REI) declined sharply between 1994 and 1999. There was a slow increase in gynecologic oncology (GO) fellows. Projections show that the numbers of practicing MFM and GO subspecialists will double by 2020, but they will be serving a 20% larger female population in the United States. Numbers of practicing REI subspecialists will increase slowly. Conclusion: The number of fellows in GO continues to enlarge progressively though slightly, whereas those in MFM and REI have fallen sharply in recent years. Among four possible factors affecting growth or decline, the ones that seem most important are existing career opportunities for both generalist and subspecialist obstetrician-gynecologists and the length of subspecialty education.

Forty pregnant women (28 to 32 weeks' gestation) were given low-dose aspirin therapy (81 mg/day) from the time of enrollment until delivery; circulating eicosanoid levels and angiotensin II pressor responses were measured before and after 1 week of aspirin therapy. Subsequent clinical outcome was correlated with these results. All women had significant reductions in serum and plasma thromboxane B2 levels with aspirin treatment (p less than 0.01). Eleven women who remained sensitive to the pressor effects of angiotensin II (effective pressor dose less than 10 ng/kg/min) after 1 week of low-dose aspirin treatment exhibited significant decreases (p less than 0.05) in plasma 6-keto-prostaglandin F1 alpha (264 +/- 119 vs 161 +/- 31 pg/ml, mean +/- SD) and prostaglandin E2 (476 +/- 174 vs 351 +/- 112 pg/ml) levels. In contrast, patients who were either nonsensitive (refractory) to angiotensin II (n = 18; greater than or equal to 10 ng/kg/min) before aspirin or became nonsensitive after aspirin administration (n = 11) had no change in either plasma 6-keto-prostaglandin F1 alpha or prostaglandin E2 concentrations. The occurrence of pregnancy-induced hypertension was 100% in the women who remained angiotensin II sensitive during aspirin therapy as compared with 36% and 39% in the other two groups (x2 = 16.14; p less than 0.001). Thus during low-dose aspirin therapy a failure to develop refractoriness to infused angiotensin II is associated with a nonselective inhibition of eicosanoids and the almost certain development of pregnancy-induced hypertension. These observations may reflect a basic defect in vascular adaptation to pregnancy.

Objective: The purpose of this study was to report the clinical experience collated from the 1995 and 1997 case list summary sheets of United States and Canadian active candidates who were completing the American Board of Obstetrics and Gynecology oral examination for the first time. Study Design: Data from the case list summary sheets were entered into a computerized database and collated. Data from active candidates who had subspecialty training and from other international graduates were excluded. Results: The difference in the ratio of men to women candidates between 1995 and 1997 was statistically significant ( P =.02). Both years, 31% of the major operations were hysterectomies, of which 60% and 62.5%, respectively, were performed through an abdominal incision. The mean total cesarean delivery rate was 20.5% in 1995 and 19.7% in 1997. The ratio of primary to repeat cesarean deliveries was 2 to 1 in both years. The ratio of forceps to vacuum extraction deliveries was 3:7 in 1995 and 2:5 in 1997. Conclusion: This data set provides a national overview of the clinical experiences of a relatively homogeneous group of practicing obstetrician-gynecologists who have recently completed their training.(Am J Obstet Gynecol 2001;185:1429-32.)

A case-control study was performed in eight pairs of women to determine whether preeclamptic women developed abnormalities in minor hemoglobins, glycolytic enzymes, or other blood components that might provide insight into the pathophysiology of preeclampsia, or that in combination might be used as a marker for the condition. These variables and standard clinical tests were analyzed as discriminators between preeclamptic and control women. The subjects were matched for age, ethnicity, parity, and gestational age. Blood samples were taken at the time of diagnosis of preeclampsia and at comparable gestational ages for matched normal controls. Variables differing significantly between groups included increases in uric acid (UA), low-density lipoproteins (LDL), phosphoglycerate kinase (PGK), and mean platelet volume (MPV), and decreases in glyceraldehyde phosphate dehydrogenase (G3PD) in preeclamptic women compared to normal controls. Discriminant analysis revealed the following function to separate the groups: 0.7764 (UA) + 0.8086 (PGK) -0.7032 (G3PD) + 0.1399 (LDL) -0.2386 (MPV). A discriminant score of > or = 275 indicated a > or = 90% probability of preeclampsia. The results are consistent with perturbations in red cell glycolysis in preeclampsia. Further prospective studies are warranted to test the efficacy of this discriminant function in predicting preeclampsia.

The purpose of our study was to evaluate the hypothesis that pregnancy is associated with decreased platelet-activating factor-acetylhydrolase activity in women with normotension, but not in women with hypertension.We evaluated plasma platelet-activating factor-acetylhydrolase activity in normal nonpregnant women (n = 10), normal pregnant women (n = 24), pregnant women with pregnancy-induced hypertension-preeclampsia (n = 7), and a group of men with normotension (n = 10).Platelet-activating factor-acetylhydrolase activity was lower at 32 weeks of gestation during normal pregnancies compared with nonpregnant controls (p0.001); however, in women with pregnancy-induced hypertension-preeclampsia, platelet-activating factor-acetylhydrolase activity was not decreased. Platelet-activating factor-acetylhydrolase activity in men was higher than in all women (p0.01).Pregnant women with normotension may be refractory to pressor agents such as angiotensin II in part because of the decrease in plasma platelet-activating factor-acetylhydrolase activity, which results in an increase in platelet-activating factor. In contrast, enzyme activity is not decreased in pregnant women with hypertension, who have increased sensitivity to various pressor agents.

Birth certificates comprise an important source of data on the prevalence of genetic conditions and for monitoring possible teratogens in the population. Investigators have found wide variability (12 to 100%) in the accuracy of reporting. In a large public hospital, of those congenital anomalies detected at birth, only 5.4% were recorded on the birth certificate. This is one of the lowest rates ever reported. An underreporting correction factor may be applied if congenital anomalies are distributed randomly with respect to reporting status, and the rate of reporting is sufficient to comprise a valid sample for estimating a correction factor (that is, 20% or more reported). In this study, factors such as numbers or types of anomalies, race, infant birthweight, or estimated gestational age did not significantly influence the rate of birth certificate reporting. Thus, our data satisfied the first but not the second criterion for derivation of a correction factor. In conducting epidemiologic studies, birth certificate data should be used with: (1) great caution; (2) a system of validation with the medical record to estimate the degree of underreporting and to derive a correction factor; and (3) a priori knowledge that underreporting of congenital anomalies on this document is highly prevalent.

• A clinically distinct constellation of major and minor anomalies, termed the fetal alcohol syndrome, occurs among infants whose mothers abuse alcohol during pregnancy. In addition, significantly higher rates of pregnancy complications, including perinatal deaths and fetal growth retardation, occur among these women and their offspring. We studied the medical records of 40 infants born to 38 alcohol abusers and the frequency of characteristics associated with fetal alcohol syndrome. Physical examinations of 6 infants revealed primary features consistent with a diagnosis of fetal alcohol syndrome. Postnatal growth and development were very poor in 17 (50%) of 34 liveborn alcohol-exposed infants. The diagnosis of fetal alcohol syndrome did not appear in the medical records of any of these infants despite the fact that the mothers' obstetric records included a history of alcohol abuse during pregnancy. This finding emphasizes the importance of good communication between obstetric and pediatric medical staff at this hospital, particularly when providing care for pregnant women and newborn infants at high risk for complications due to maternal alcohol or other drug abuse. (AJDC. 1990;144:1142-1146)

Objective: The purpose of our study was to evaluate the hypothesis that pregnancy is associated with decreased platelet-activating factor-acetylhydrolase activity in women with normotension, but not in women with hypertension. Study Design: We evaluated plasma platelet-activating factor-acetylhydrolase activity in normal nonpregnant women ( n = 10), normal pregnant women ( n = 24), pregnant women with pregnancy-induced hypertension-preeclampsia ( n = 7), and a group of men with normotension ( n =10). Results: Platelet-activating factor-acetylhydrolase activity was lower at 32 weeks of gestation during normal pregnancies compared with nonpregnant controls ( p p Conclusion: Pregnant women with normotension may be refractory to pressor agents such as angiotensin II in part because of the decrease in plasma platelet-activating factor-acetylhydrolase activity, which results in an increase in platelet-activating factor. In contrast, enzyme activity is not decreased in pregnant women with hypertension, who have increased sensitivity to various pressor agents.

The transfer constants of conversion of maternal plasma dehydroisoandrosterone sulfate to estradiol ( BU DS − E 2 ) and to 16 α OH-dehydroisoandrosterone sulfate ( BU DS − 16 OHDS ) and of maternal plasma 16 α OH-dehydroisoandrosterone sulfate to estriol ( BU DS − 16 OHDS − E 3 ) were measured in women late in pregnancy. The mean BU DS − 16 OHDS − E 3 , 0.17, was considerably less than the mean BU DS − E 2 , 0.29. However, the extent of 16 α -hydroxylation of maternal plasma dehydroisoandrosterone sulfate was great, the mean BU DS − 16 OHDS being 0.36.

Loss to follow-up is a major problem in indigent inner-city populations. We evaluated a large, well-described, inborn indigent population of high-risk infants (HRI) and control infants (CI) to assess possible selection biases in loss to follow-up at one year adjusted age. Serial clinic visits, phone calls, and letters and payment of $20.00 for attending at 1 year was used to minimize patient loss. Yet, the 1 year loss rate was high, and among HRI, greater for ventilator-treated infants greater than 1500 g birthweight (71/114; 62%) than for ventilator-treated very-low-birthweight (VLBW; less than 1500 g) infants (39/108; 36%) or non-ventilated VLBW infants (62/145; 43%) (P less than 0.05). Multivariate analyses indicated that those lost to follow-up were at no greater risk of a poor outcome on the basis of prenatal and perinatal medical and socioeconomic findings than were those in the same risk group (HRI or CI) or subgroup of HRI who were examined at 1 year. In a review of hospital records, similar rates of hospitalization and neurologic problems during infancy were identified for HRI examined and HRI lost to follow-up. The identification of such morbidity during infancy may be less complete for HRI lost to follow-up than for those examined. Thus, the high frequency of deficits observed in follow-up evaluation of indigent HRI is unlikely to result from loss of unaffected infants.

Indomethacin administration has produced decreases in uteroplacental blood flow in several animal studies; therefore, it has been suggested that the maintenance of uterine blood flow is critically dependent on the continued synthesis of vasodilating prostaglandins. However, vasoconstriction following indomethacin administration may be due to mechanisms other than reduced prostaglandin synthesis. We administered indomethacin (2, 5, or 10 mg/kg) intravenously to seven unanesthetized sheep in late pregnancy and determined the time courses of the uteroplacental and systemic hemodynamic responses, comparing these to the concurrent changes in circulating prostaglandins. Indomethacin administration resulted in rapid increases in systemic and uteroplacental vascular resistance (80% to 100%) and mean arterial pressure (approximately 30%) and in decreases in systemic (approximately 30%) and uteroplacental (0% to 30%) blood flows within 5 minutes. Vasoconstriction was transient, however, and after 60 minutes there was no evidence of uterine or systemic vasoconstriction, although systemic and uterine plasma prostaglandin levels remained reduced for 180 minutes. Thus substantial inhibition of prostaglandin synthesis existed without evidence of concurrent systemic or uteroplacental vasoconstriction, suggesting that uterine blood flow is not directly dependent on maintained prostaglandin synthesis in unstressed pregnant sheep. Furthermore, the transient indomethacin-induced vasoconstriction may not be due to inhibition of prostaglandin synthesis.

An optimal assay system for the measurement of GC activity in subcellular fractions of human placenta homogenates was developed. MN2+ was more effective than Mg2+ as a cofactor and, in addition, it markedly potentiated the Mg2+-dependent GC activity. The apparent optimal temperature for GC activity was 45 degrees C and the pH optimum was in the range of 7.5 to 8.3. The apparent Km of Mn2+-dependent GC for GTP was 0.1 and that of MG2+-dependent GC for GTP was 0.4 mm. More than 95 per cent of GC activity was associated with the 100 000 X g supernatant fraction. ATP at a concentration of 0.5 mm inhibited GC activity by 50 per cent. The Mn2+-dependent GC activity was inhibited by p-hydroxymercuriphenyl sulphonate at concentrations between 10 and 50 micrometers; this inhibition was reversed, in part, by dithiothreitol at concentrations of 150 to 500 micrometers to approximately one-fifth the activity of control values. In addition, we found that dithiothreitol was an inhibitor of GC activity. Studies on the responsiveness of placental GC to nucleophilic compounds indicated that phenylhydrazine was the most potent stimulus, while hydroxylamine, hydrazine, sodium azide, sodium nitrite and sodium nitroprusside were less potent. Placental GC was unaffected by alpha- and beta-adrenergic agonists or by cholinergic agonist, as well as by steroids produced by the placenta.

Ninety-three per cent of nulliparous, normotensive young women who subsequently developed pregnancy-induced hypertension demonstrated an increase in diastolic blood pressure of at least 20 mm. Hg when turned from the lateral recumbent to the supine position between the twenty-eighth and thirty-second weeks of gestation. Conversely, 91 per cent of women who did not demonstrate such a rise in diastolic blood pressure when turned to the supine position did not become hypertensive during that pregnancy. Additionally, very close correlations were demonstrated between: (1) a positive supine pressor response and increased sensitivity to intravenously infused angiotensin II, and (2) a negative supine pressor response and increased resistance to angiotensin II.

In the present investigation, we evaluated the effect(s) of long-term hypertension and pregnancy-induced , hypertension in women on the activity of the adrenals of their fetuses. We measured dehydroisoandrosterone sulfate, cortisol, and lipoprotein-cholesterol in umbilical cord plasma of newborn infants delivered (30 to 41 weeks' gestation) of 129 women whose pregnancies were uncomplicated and of 98 women with pregnancy-induced or long-term hypertension. Umbilical cord plasma levels of cortisol were similar in both groups of newborn infants at each gestational period. Fetal plasma levels of dehydroisoandrosterone sulfate also were similar in both groups at 30 to 33 weeks of gestation but were significantly reduced in newborn infants of hypertensive women who were delivered between 34 and 41 weeks of gestation compared with those of newborn infants of normal women who were delivered at a similar gestational age. At term, umbilical cord plasma levels of total cholesterol and low-density lipoprotein-cholesterol were significantly higher in the newborn infants of hypertensive women compared with those levels in newborn infants of normotensive women; fetal plasma levels of high-density lipoprotein-cholesterol and very low-density lipoprotein-cholesterol were similar in both groups of newborn infants. The lowest plasma levels of dehydroisoandrosterone sulfate and the highest plasma levels of total cholesterol and low-density lipoprotein-cholesterol were found in newborn infants of women with the most severe pregnancy-induced hypertension. Based on these findings, we conclude that maternal hypertension (1) effects a decrease in the rate of steroidogenesis of the fetal zone of the fetal adrenal cortex but does not act in a similar manner to effect steroidogenesis of the neocortical zone and (2) leads to hypercholesterolemia in the fetus as a consequence of reduced adrenal utilization of low-density lipoprotein-cholesterol. In addition, the effects of pregnancy-induced hypertension appear to be manifest in the fetus late in pregnancy at a time when the fetal adrenal normally undergoes an accelerated rate of growth and steroid biosynthesis.

The concentration of 5 alpha-pregnane-3,20-dione in peripheral blood of pregnant women is higher than that found in blood obtained from nonpregnant women throughout the luteal phase of the ovulatory cycle. The in vitro synthesis of 5 alpha-reduced pregnanes from [3H]progesterone by placental tissue was investigated using tissue minces and homogenates in the presence of added nicotinamide-adenine dinucleotide phosphate. The metabolites, [3H]5 alpha-pregnane-3,20-dione and [3H]3 beta-hydroxy-5 alpha-pregnan-20-one, were isolated and characterized employing a combination of chromatographic techniques, derivative formation, and crystallization with authentic [14C]5 alpha-pregnane-3,20-dione and [14C]3 beta-hydroxy-5 alpha-pregnan-20-one to constant 3H:14C ratios. In short-term incubations with placenta homogenates, the apparent pH optimum for the synthesis of 5 alpha-pregnane-3,20-dione was 8.8. There was no evidence for the formation of 5 beta-reduced pregnanes from [3H]progesterone by placental tissue. The in vitro metabolism of [3H]progesterone by minces of five term placentas, during 1 hour incubations at pH 7.4, was studied. The rate of formation of 5 alpha-pregnane-3,20-dione varied from 109 to 197 pmoles/gm placental tissue/hr.

The plasma concentrations of progesterone and 5-alpha-pregnane-3,20-dione (5-alpha-dihydroprogesterone) were measured from as early as 12 weeks through 41 weeks of gestation in primigravid women. Two groups of primigravid women were assessed, those with uncomplicated pregnancies and those who developed pregnancy-induced hypertension. Plasma levels of progesterone and 5-alpha-dihydroprogesterone rose progressively throughout gestation in both groups of women. The ratio of the level of progesterone to that of 5-alpha-dihydroprogesterone in individual plasma samples of women with uncomplicated pregnancies was 7.0 from 12 to 15 weeks' gestation while at 35 to 41 weeks' gestation the ratio had declined to 4.6. Similar results were obtained in plasma samples of women who ultimately developed pregnancy-induced hypertension. Since no differences in plasma levels of progesterone or 5-alpha-dihydroprogesterone were detected between primigravid women with uncomplicated pregnancies and those who developed pregnancy-induced hypertension, we conclude that neither progesterone nor 5-alpha-dihydroprogesterone concentrations in plasma are of value in identifying women at risk of developing pregnancy-induced hypertension.

In gravid women who are destined to develop pregnancy-induced hypertension (PIH), normal pregnancy-associated refractoriness to the pressor effects of administered angiotensin II (A-II) is lost several weeks before the onset of hypertension. From a study of the determinants of A-II pressor responsiveness in normal gravid women, it appears likely that the loss of resistance to A-II is principally unrelated to plasma renin activity or to plasma A-II levels. However, it recently has been shown that the vascular refractoriness to A-II in normal women can be reduced significantly by the administration of the prostaglandin synthetase inhibitors, indomethacin or aspirin. In seven women who had developed PIH and who had lost their refractoriness to A-II, the infusion of 5alpha-pregnan-3,20-dione (5alpha-DHP) was associated with restoration of refractoriness to the pressor effects of A-II. Moreover, in five normotensive gravid women beyond 28 weeks' gestation in whom the refractoriness to A-II was reduced by the administration of indomethacin, the intravenous infusion of 5alpha-DPH was associated with restoration of refractoriness to the pressor effects of A-II. These observations are consistent with the view that a progesterone metabolite(s) may be important in the maintenance of normal blood pressure during human pregnancy.

Discussed in this article are the effects of pregnancy-induced hypertension on the renin-angiotensin-aldosterone system; the possible role of prostanoids, deoxycorticosterone, and deoxycorticosterone sulfate in blood pressure control; and the effect of pregnancy-induced hypertension upon the endocrinology of the maternal-fetal-placental unit.

Risk factors for pregnancy-induced hypertension (PIH) were assessed using a computerized data base on 28,838 women delivering at Parkland Memorial Hospital between 1978 and 1980. Of the total sample, 5,190 (18%) developed PIH, defined as diastolic blood pressure > 90 mmHg on more than one occasion measured at least 8 hours apart. Odds ratios for potential risk factors for PIH, as selected from a literature review, were estimated using multiple logistic regression. Our results were indicative that: (1) Age had a linear (not U-shaped) relation with PIH after adjusting for parity; (2) PIH was twice as likely to occur if chronic hypertension were present, controlling for all other variables; (3) Diabetes did not have a significant association with PIH, controlling for chronic hypertension and other variables; and (4) Heart disease, renal disease, race and multiple gestation had important independent effects on PIH.

The plasma concentration of deoxycorticosterone (DOC) was determined serially in a large group of primigravid women from 10 weeks' gestation to term. The plasma level of DOC in women whose pregnancies were uncomplicated (n = 44) was 234 +/- 33 pg/ml (mean +/- SE), at 10 to 14 weeks' gestation, a level two times that of nonpregnant subjects. The plasma level of DOC in these women rose to 778 +/- 65 pg/ml at 23 to 26 weeks' gestation, and at term (39 to 42 weeks) was 1,309 +/- 155 pg/ml. The plasma levels of DOC in women (n = 31) who eventually developed pregnancy-induced hypertension (PIH) were similar to those in the women who remained normal at all stages of pregnancy. We also found that, in women with normal pregnancies as well as in all stages of pregnancy. We also found that, in women with normal pregnancies as well as in women destined to develop PIH, the plasma concentration of DOC fluctuated in a manner parallel to that of progesterone throughout gestation; however, changes in the plasma level of DOC did not mirror those of cortisol. These data suggest that excessive plasma levels of DOC are not necessarily associated with the development of PIH. These data also support the view that, in pregnant women, a fraction of circulating DOC may arise via extra-adrenal 21-hydroxylation of progesterone rather than through adrenal secretion.

In the present study, the metabolic clearance rate of dehydroisoandrosterone sulfate (MCR DS ) decreased in normotensive gravidas during short-term studies utilizing angiotensin II–induced elevation of blood pressure. Therapy with hydralazine hydrochloride in chronic hypertensive gravidas resulted in a decrease in blood pressure and an accompanying decrease in the MCR DS , A variable response was observed in the apparent volume of distribution of DS (AVD DS ) during therapy with hydralazine hydrochloride. Decreases in MCR DS also occurred in chronic hypertensive gravidas following therapy with 40 mg. of intravenously administered furosemide despite a failure of blood pressure to be altered. The AVD DS increased in four of five patients receiving furosemide, suggesting a possible direct action of furosemide upon vascular smooth muscle.

Refractoriness to infused angiotensin II is characteristic or normal human and ovine pregnancy; the mechanisms responsible are unclear. In this study, we sought to ascertain in gravid sheep whether hypertonic saline solution alters the vascular responses to angiotensin II, as in gravid women, and to compare the responses of the systemic and uteroplacental vasculature. Dose-response curves were determined. Mean arterial pressure and systemic vascular resistance increased in a dose-dependent fashion before and after hypertonic saline solution; responses were greater after hypertonic saline solution (p less than 0.01). Responses of cardiac output, heart rate, uterine vascular resistance, and uterine blood flow also were dose-dependent, but were unchanged after hypertonic saline solution. Plasma renin activity fell 45% after hypertonic saline solution. Treatment with hypertonic saline solution results in increased pressor responses to angiotensin II that are not a reflection of altered baroreceptor or chemoreceptor reflexes or of the response in the uteroplacental vascular bed. Rather, the increased systemic vascular responsiveness to angiotensin II after hypertonic saline solution appears to be a reflection of other mechanisms, such as alterations in vessel wall dynamics or receptor affinity.

In in vitro studies it was found that, in the presence of added NADPH, the human placenta metabolizes progesterone to 20alpha-hydroxy-4-pregnen-3-one at increasing rates as pregnancy advances. A fivefold increase in 20alpha-hydroxysteroid oxidoreductase activity is observed in term placentas compared with the enzymic activity of placentas of 12 to 20 weeks' gestation (368 +/- 53 pmoles/mg protein/hr vs 71 +/- 8 pmoles/mg protein/hr). The 5alpha-reductase and 3beta-hydroxysteroid oxidoreductase activities were similar in placentas obtained from early and late human pregnancies.

The present study was done to map the metabolic pathways and rates of maternal plasma clearance of dehydroisoandrosterone sulfate (MCRDS) in pregnancy. In the present study, maternal plasma dehydroisoandrosterone sulfate (DS) metabolism was largely accounted for by two major pathways not present or not prominent in the nonpregnant woman. The first major pathway was clearance of maternal plasma DS by placental aromatization of DS to form estradiol (E2). This pathway accounted for approximately 35 per cent of the total clearance. The second major pathway of metabolism of maternal plasma DS was by 16 alpha-hydroxylation within the maternal compartment. This pathway accounted for approximately 32 per cent of maternal plasma DS clearance. Two other minor pathways of DS metabolism, that is, loss to the fetus and excretion as unaltered DS into urine, accounted for less than 1 per cent of total metabolism in each instance. The final pathway of DS metabolism was excretion as neutral steroids such as urinary 17-ketosteroids and other undefined losses. By combining the rate of DS clearance (MCRDS) from maternal plasma via all pathways with that fraction of DS removed uniquely by placental conversion of DS to estradiol (DS leads to E2), the placental clearance of DS leads to E2 (PCDSE2) may be measured. The measurement of PCDSE2 may be expected to reflect uteroplacental perfusion and as such may provide an investigative tool capable of assessing the dynamics of uteroplacental function in a variety of clinical conditions.

Hospitalization of women with pregnancy-induced hypertension is beneficial in improving pregnancy outcome, but how it affects this physiologic process is not clear. In the present investigation, we evaluated pressor responsiveness to angiotensin II in 62 hospitalized women with pregnancy-induced hypertension. Although each of the women became normotensive, at least transiently, all remained sensitive to the pressor effects of angiotensin II. Thus, the beneficial effect of hospitalization on women with pregnancy-induced hypertension cannot be attributed to a decrease in the responsiveness to the action of angiotensin II.

The relation between pregnancy-induced hypertension and reproductive history was assessed in 29,484 women receiving obstetric care at Parkland Memorial Hospital. The incidence of pregnancy-induced hypertension was 25.4% in primigravid women, somewhat lower (22.3%) in women whose only previous pregnancy terminated in abortion, and much lower (10%) in women who carried two or more successive pregnancies to viability.

The present study was designed to (1) outline, in a prospective manner, vascular responsiveness to angiotensin II (A-II) in gravidas with essential hypertension and (2) ascertain if increased sensitivity to infused A-II could be detected before worsening of hypertension developed in those women who were destined to develop superimposed pregnancy-induced hypertension (PIH). Sixty-three women with chronic essential hypertension were studied sequentially throughout pregnancy and two groups of patients were defined on the basis of clinical outcome and serial measurements of vascular reactivity to exogeneously administered A-II. The first group consisted of 29 gravidas with chronic hypertension alone and the second group was composed of 34 patients with chronic hypertension who were destined to develop superimposed PIH. Vascular resistance to infused A-II (more than 7 ng. per kilograms per minute required to increase diastolic blood pressure 20 mm. Hg) was observed from weeks 21 to 27 of gestation in both groups of patients. In the gravidas with essential hypertension alone, resistance to A-II persisted throughout the remainder of pregnancy. However, in those women destined to develop PIH, an increased sensitivity to A-II developed after week 27 of gestation and the differences in mean values between the two groups of patients became highly significant after week 30 of gestation (P less than 0.025). although individual determinations obtained in both groups of patients between weeks 28 and 32 of preganncy suggested that pressor responsiveness to A-II might be used as a screening technique to identify those women destined to develop PIH, additional studies conducted between weeks 28 and 32 of gestation will be required before the efficacy of such a screening technique is clearly established.

Summary The activation of placental AC by either Mg 2+ or Mn 2+ , in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn 2+ enhanced maximally the NaF-stimulated Mg 2+ -dependent AC activity. The apparent K m of Mg 2+ -dependent AC for ATP was 0.4 m M , with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg 2+ -dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 μM. In the presence of GMP-P(NH)P (10 μm) the kinetics of the AC dependence on Mg + ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (> 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by β-adrenergic agonists. Placental AC activity was inhibited by p -hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg 2+ -dependent AC was inhibited by 0.5 mm phenylhydrazine (95 per cent). Mg 2+ -dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 μm. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17β, 2-hydroxyoestreone, 2-hydroxyoestradiol-17β, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg 2+ -dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.

In a continuing effort to define the origin of and the regulation of the production of deoxycorticosterone, we measured deoxycorticosterone and progesterone in the umbilical cord plasma of 16 anencephalic fetuses and newborn infants (21 to 45 weeks' gestation) and deoxycorticosterone, progesterone, 17 beta-estradiol, and estriol in the plasma of 18 women pregnant (16 to 45 weeks) with an anencephalic fetus. Whereas umbilical cord plasma levels of progesterone in the anencephalic fetuses were similar to those of normal abortuses and newborn infants, those of deoxycorticosterone (1.3 +/- 0.21 ng/ml, mean +/- SE) were significantly lower (P less than 0.001) than those in normal abortuses and newborn infants delivered between 31 and 42 weeks' gestation (3.94 +/- 0.26 ng/ml). We found that plasma levels of deoxycorticosterone were significantly correlated (P less than 0.001) to those of progesterone in women pregnant with an anencephalic fetus, as well as in women pregnant with a normal fetus. Plasma levels of deoxycorticosterone (range = 0.14 to 0.92 ng/ml) in women pregnant with an anencephalic fetus were significantly lower than those in women pregnant with a normal fetus; plasma levels of progesterone were similar in both groups. The plasma levels of 17 beta-estradiol and of estriol were extremely low in women pregnant with an anencephalic fetus compared with those in women with a normal fetus and did not vary as a function of gestational age. In one subject who was pregnant with an anencephalic fetus, we found that estrogen treatment (100 mg of diethylstilbestrol/day) for 6 days caused a progressive increase in the serum levels of deoxycorticosterone and in the ratio of the concentration of concentration of deoxycorticosterone to that of progesterone in serum. Both the serum levels of deoxycorticosterone and the ratio of the concentration of deoxycorticosterone and in the ratio of the concentration of deoxycorticosterone to that of progesterone declined after cessation of estrogen treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

The metabolism of androstenedione (A) by the placenta in late pregnancy and the early puerperium was studied. The metabolic clearance rate of A (MCR-A) was increased in pregnant women, 2,825 +/- 207 L/24 hr (mean +/- SEM), compared to 2,020 +/- 140 L/24 hr in nonpregnant women of similar body weight. The immediate puerperal MCR-A was 2,538 +/- 50 L/24 hr. Therefore, approximately 10% of maternal plasma A was cleared by the placenta. In the latter half of pregnancy, the extent of conversion of maternal plasma A through estradiol formation, (rho)AE2, was increased, whereas in the immediate puerperium it was normal, 0.018. Moreover, 90% of aromatase activity was attributed to the placenta in late pregnancy. From these data, we computed that the placental clearance rate of A through estradiol (PCAE2) from whole blood was 497 +/- 41 ml/min in women with a single fetus and 691 +/- 102 ml/min in women with twin fetuses. Thus, it appears that the PCAE2 is a sensitive index of maternal-placental perfusion.

To compare maternal-infant interactions in high- and low-risk groups, we observed infants who had required neonatal intensive care and otherwise similar infants with normal perinatal histories in a follow-up clinic at one year adjusted age. The developmental level as assessed by the Bayley Scales of Infant Development was significantly lower for the high-risk infants than for the control infants at one year of age. Principal component analyses were used to define interaction patterns in each of five situations. Principal component analyses allow a more meaningful analysis of interrelated maternal and infant behaviors than do standard statistical analyses and minimize the likelihood of misleading ‘significance’ findings resulting from multiple comparisons. Prior to being examined, mothers of control infants were more likely to adopt an ‘en face’ position, play with, comfort, talk to, and smile at their infants than were mothers of high-risk infants. Control infants were more likely to smile in return. These differences between control and high-risk mother-infant dyads disappeared when the infants' developmental level was statistically controlled. Group differences in maternal-infant interactions independent of the infants' developmental level were observed in only one situation (collection of blood). Specific medical risk factors had little relation to findings at one year. Maternal-infant interaction should be interpreted in relation to the postconceptional and developmental age as well as the postnatal age of the infant.

Normally, women become refractory to the pressor effects of infused angiotensin-II (A-II) early in pregnancy. Gravid women destined to develop pregnancy-induced hypertension (PIH) lose this refractoriness to A-II several weeks prior to the detection of hypertension. Normal pregnant women also lose their A-II refractoriness after treatment with prostaglandin synthetase inhibitors and, in this regard become similar to gravid women who are destined to develop PIH. From this observation, we have concluded that a prostaglandin(s) or a prostaglandin-related substance(s) is likely involved in the mediation of vascular reactivity to A-II during pregnancy. The present study was conducted to ascertain if control of vascular reactivity during pregnancy also involves the cyclic nucleotides. Since theophylline is known to inhibit the action of phosphodiesterase, an action that results in increased cellular levels of cyclic 3',5'-adenosine monophosphate (cAMP), we evaluated the effective pressor dose of A-II before and after the administration of theophylline to women with mild PIH who were beyond the 28th week of gestation. The effective pressor dose of A-II in these women with PIH before theophylline treatment was 7.3 +/- 1.4 ng. times kg.(-1) times min.(-1) (mean and standard error). Following treatment of these women with the equivalent of 500 mg. of theophylline daily for four days, the effective pressor dose of A-II was 16.7 +/- 3.8 ng. times kg.(-1) times min.(-1) (p less than 0.025). These findings are consistent with the view that a prostaglandin(s) synthesized in the arteriole may modulate the vascular refractoriness to A-II by altering the intracellular level of cAMP in vascular tissues.

We have suggested that the placental clearance of maternal plasma dehydroisoandrosterone sulfate (DS) through estradiol (E2) formation (PC-DSE2) is reflective of uteroplacental blood flow (F). Clewell and Meschia13 suggested that PC-DSE2 is related to F as follows: Cobs = F(1-e-C/F), where Cobs = PC-DSE2 and C = total placental clearance of maternal plasma DS. This equation contains two unknown quantities, F and C. To solve the equation, Clewell and Meschia assumed that C was constant. Using 19.7 ml/min for C, they allowed PC-DSE2 to vary widely and computed F. Upon finding that F was unrealistically low for some values of PC-DSE2, they concluded that reductions in PC-DSE2 do not reflect alterations in uteroplacental blood flow. In the analysis of the relationship of F to PC-DSE2, it is important to know the value of C. Since the direct measurement of C is not possible at this time, we have evaluated C by measuring the difference between the metabolic clearance rate of DS (MCR-DS) prior to and immediately following delivery. Any change in MCR-DS before and after delivery should be a reflection of the amount of maternal plasma DS cleared by the placenta through all metabolic routes including PC-DSE2, providing nonplacental clearances of maternal plasma DS before and immediately after delivery are the same. We measured MCR-DS and PC-DSE2 in 15 pregnant women within 5 days before delivery and repeated the MCR-DS measurement in these women beginning 90 minutes after delivery. Among these 15 women, C ranged from a low of 4.7 ml/min in a woman with severe pre-eclampsia to a high of 28.5 ml/min in a woman with twins. In addition to the finding that C varied widely, it was also ascertained that PC-DSE2 was positively correlated with C (r = 0.908; p less than 0.001). The finding that low or high values for PC-DSE2, observed in complicated pregnancies, were associated with similar changes in C is suggestive that a change in PC-DSE2 is reflective of a change in uteroplacental blood flow.

The metabolic clearance rate (MCR) of dehydroisoandrosterone sulfate (DS) was determined in nonpregnant women, normal pregnant women, and pregnant women with pre-eclampsia. The MCR of DS in normal pregnant women was markedly elevated compared with that of nonpregnant subjects, while in those women with severe pre-eclampsia the MCR DS was much lower. A prospective study in teen-age primigravid subjects demonstrated that, in those who remained normal, a progressive increase in the MCR DS continued until delivery. In those young women who ultimately developed pre-eclampsia, the MCR DS initially rose to a degree comparable to that of or greater than that observed in those subjects who remained normal; however, rather than the MCR DS continuing to increase progressively until delivery, in those subjects who ultimately developed pre-eclampsia, the MCR DS began to decrease 3 to 4 weeks prior to the development of clinically evident disease. This observed decline in MCR DS continued thereafter for the remainder of pregnancy.

The effect of Argo gloss starch and of 2 popular clays on the absorption of a standard dose of ferrous iron was measured in women with iron-deficiency anemia and in normal subjects. The ingestion of sizable amounts of the starch or clays just prior to the iron did not appreciably impair iron absorption. Therefore, if the laundry starch contributes to the development of iron-deficiency anemia, it most likely does so simply by providing calories without iron rather than by impairing iron absorption. Although the 2 popular regional clays studied did not reduce the amount of iron absorbed, the ingestion of some clays has been demonstrated by others to do so. A red clay containing considerable iron proved to be ineffective for correcting iron-deficiency anemia.